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Effects of IL-7 on memory CD8+ T cell homeostasis are influenced by the timing of therapy in mice
Som G. Nanjappa, Jane H. Walent, Michel Morre, M. Suresh
Som G. Nanjappa, Jane H. Walent, Michel Morre, M. Suresh
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Research Article Immunology

Effects of IL-7 on memory CD8+ T cell homeostasis are influenced by the timing of therapy in mice

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Abstract

IL-7 is integral to the generation and maintenance of CD8+ T cell memory, and insufficient IL-7 is believed to limit survival and the persistence of memory CD8+ T cells. Here, we show that during the mouse T cell response to lymphocytic choriomeningitis virus, IL-7 enhanced the number of memory CD8+ T cells when its administration was restricted to the contraction phase of the response. Likewise, IL-7 administration during the contraction phase of the mouse T cell response to vaccinia virus or a DNA vaccine potentiated antigen-specific CD8+ memory T cell proliferation and function. Qualitatively, CD8+ T cells from IL-7–treated mice exhibited superior recall responses and improved viral control. IL-7 treatment during the memory phase stimulated a marked increase in the number of memory CD8+ T cells, but the effects were transient. IL-7 therapy during contraction of the secondary CD8+ T cell response also expanded the pool of memory CD8+ T cells. Collectively, our studies show differential effects of IL-7 on memory CD8+ T cell homeostasis and underscore the importance of the timing of IL-7 therapy to effectively improve CD8+ T cell memory and protective immunity. These findings may have implications in the clinical use of IL-7 as an immunotherapeutic agent to bolster vaccine-induced CD8+ T cell memory.

Authors

Som G. Nanjappa, Jane H. Walent, Michel Morre, M. Suresh

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Figure 11

IL-7 treatment during the contraction phase of the secondary response enhances CD8 T cell memory.

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IL-7 treatment during the contraction phase of the secondary response en...
One hundred days after LCMV infection, mice were challenged with recombinant Listeria monocytogenes (LM-GP33) that expresses the GP33 epitope of LCMV. LM-GP33–infected mice were treated daily with IL-7 or PBS between days 5 and 15 after challenge. On day 34 after challenge, the number of CD8 T cells in the spleen specific to the indicated LCMV epitope (NP396, GP33, and GP276) was enumerated by intracellular staining for IFN-γ as described in Methods. Flow cytometry data were analyzed to determine the percentages of CD8 T cells and IFN-γ–producing CD8 T cells in individual mice. (A) The total number of epitope-specific IFN-γ–producing CD8 T cells in the spleens of PBS- and IL-7–treated mice. (B) Percentages of CD8 T cells/spleen or percentages of epitope-specific CD8 T cells among total CD8 T cells in the spleens of PBS- or IL-7–treated mice. Note that the symbols represent data from an individual mouse.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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